Annema Wijtske, von Eckardstein Arnold, Kovanen Petri T
Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland,
Handb Exp Pharmacol. 2015;224:369-403. doi: 10.1007/978-3-319-09665-0_11.
High-density lipoproteins (HDLs) exert many beneficial effects which may help to protect against the development or progression of atherosclerosis or even facilitate lesion regression. These activities include promoting cellular cholesterol efflux, protecting low-density lipoproteins (LDLs) from modification, preserving endothelial function, as well as anti-inflammatory and antithrombotic effects. However, questions remain about the relative importance of these activities for atheroprotection. Furthermore, the many molecules (both lipids and proteins) associated with HDLs exert both distinct and overlapping activities, which may be compromised by inflammatory conditions, resulting in either loss of function or even gain of dysfunction. This complexity of HDL functionality has so far precluded elucidation of distinct structure-function relationships for HDL or its components. A better understanding of HDL metabolism and structure-function relationships is therefore crucial to exploit HDLs and its associated components and cellular pathways as potential targets for anti-atherosclerotic therapies and diagnostic markers.
高密度脂蛋白(HDL)具有多种有益作用,可能有助于预防动脉粥样硬化的发生或发展,甚至促进病变消退。这些作用包括促进细胞胆固醇流出、保护低密度脂蛋白(LDL)不被修饰、维持内皮功能以及抗炎和抗血栓作用。然而,这些作用对动脉粥样硬化保护的相对重要性仍存在疑问。此外,与HDL相关的许多分子(包括脂质和蛋白质)发挥着不同但又重叠的作用,这些作用可能会因炎症状态而受损,导致功能丧失甚至功能异常。HDL功能的这种复杂性迄今为止阻碍了对HDL或其成分独特的结构-功能关系的阐明。因此,更好地理解HDL代谢以及结构-功能关系对于将HDL及其相关成分和细胞途径作为抗动脉粥样硬化治疗的潜在靶点和诊断标志物加以利用至关重要。